rs11858860

Variant names:

• chr15-85408215-T-C
• rs11858860
• NM_007200.5:c.-12+27417T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007200.5(AKAP13):​c.-12+27417T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 151,474 control chromosomes in the GnomAD database, including 4,209 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (4209 hom., cov: 32)
• Consequence: AKAP13 NM_007200.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 3 publications found

Genes affected

AKAP13 (HGNC:371): (A-kinase anchoring protein 13) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains. The DH domain is associated with guanine nucleotide exchange activation for the Rho/Rac family of small GTP binding proteins, resulting in the conversion of the inactive GTPase to the active form capable of transducing signals. The PH domain has multiple functions. Therefore, these isoforms function as scaffolding proteins to coordinate a Rho signaling pathway, function as protein kinase A-anchoring proteins and, in addition, enhance ligand-dependent activity of estrogen receptors alpha and beta. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP13	NM_007200.5	c.-12+27417T>C		intron_variant	Intron 1 of 36	ENST00000394518.7	NP_009131.2
AKAP13	NM_006738.6	c.-12+27417T>C		intron_variant	Intron 1 of 36		NP_006729.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP13	ENST00000394518.7	c.-12+27417T>C		intron_variant	Intron 1 of 36	1	NM_007200.5	ENSP00000378026.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30957 AN: 151356 Hom.: 4204 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.196

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.205 AC: 30989 AN: 151474 Hom.: 4209 Cov.: 32 AF XY: 0.206 AC XY: 15240 AN XY: 74042

African (AFR) AF: 0.326 AC: 13330 AN: 40880

American (AMR) AF: 0.322 AC: 4915 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5170

South Asian (SAS) AF: 0.145 AC: 696 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1472 AN: 10590

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8599 AN: 67974

Other (OTH) AF: 0.194 AC: 410 AN: 2108

Alfa AF: 0.159 Hom.: 3238

Bravo AF: 0.230

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.89
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11858860; hg19: chr15-85951446;